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(Radiology. 2001;220:329-336.)
© RSNA, 2001

Gastrointestinal Imaging

Primary Biliary Cirrhosis: Clinical, Pathologic, and Helical CT Findings in 53 Patients1

Arye Blachar, MD, Michael P. Federle, MD and Giuseppe Brancatelli, MD

1 From the Department of Radiology, University of Pittsburgh Medical Center, UPMC-Presbyterian Hospital, 200 Lothrop St, Pittsburgh, PA 15213. Received October 24, 2000; revision requested December 12; revision received February 8, 2001; accepted February 26. G.B. supported by the Nicholas Green Fulbright Grant. Address correspondence to M.P.F. (e-mail: federle@pitt.edu).


   ABSTRACT
TOP
 ABSTRACT
INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 
PURPOSE: To evaluate and compare clinical, pathologic, and helical computed tomographic (CT) findings of primary biliary cirrhosis (PBC).

MATERIALS AND METHODS: The authors reviewed the medical records and CT scans of 53 patients who underwent evaluation, treatment, and orthotopic liver transplantation (OLT) at their institution. All patients underwent helical multiphase CT (total, 98 abdominal CT scans; range, one to five scans per patient). Multiple epidemiologic, clinical, and morphologic criteria were evaluated. Advanced disease was defined as hepatic insufficiency leading to OLT within the subsequent 2 years. Clinical and morphologic features were evaluated and compared in the advanced and less advanced cases of PBC.

RESULTS: Common and characteristic findings included the following: 45 (85%) of the 53 patients were women with the onset of disease (diagnosis) in middle age (mean, 50.7 years; range, 26–71 years). The average time from diagnosis to OLT was 6.1 years (range, 1.5–20.0 years). CT findings in advanced PBC often resembled those seen in other forms of cirrhosis, with a small heterogeneously attenuating liver, varices, and splenomegaly. The liver in less advanced disease was usually enlarged or normal in size, with a smooth contour, little atrophy, and lacelike fibrosis and regenerative nodules in nearly one-third of the livers. Patients with less advanced disease frequently had varices (n = 33 [62%]) and ascites (n = 13 [24%]). Lymphadenopathy was seen in 47 (88%) patients. Hepatocellular carcinoma was found in four (8%) patients, two of whom also had chronic hepatitis C. During a follow-up period of 5–72 months (median, 46 months; mean, 42 months) after OLT, only two patients experienced recurrence of PBC.

CONCLUSION: PBC is an important cause of liver failure, with distinctive clinical and CT findings that may assist diagnosis and allow adequate treatment. CT can demonstrate varices and ascites before frank cirrhosis is evident and can help evaluate the progression of the disease.

Index terms: Liver, cirrhosis, 761.288 • Liver, CT, 761.12111, 761.12112, 761.12114, 761.12115 • Liver, fibrosis • Liver, transplantation, 761.451


   INTRODUCTION
TOP
 ABSTRACT
 INTRODUCTION
MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 
Primary biliary cirrhosis (PBC) is a chronic progressive cholestatic liver disease that is the cause of 1%–2% of deaths from cirrhosis (1,2), and it constitutes the third most common indication for liver transplantation in adults. PBC is characterized by the destruction of small intrahepatic bile ducts, portal inflammation, and progressive scarring. The typical patient is a middle-aged woman presenting with symptoms of fatigue and pruritus and laboratory test evidence of cholestasis. The cause of PBC is unknown, but it is probably due to an inherited abnormality of immunoregulation. Serum antimitochondrial antibody tests are highly sensitive and specific for PBC (3), and PBC is often associated with other autoimmune diseases, such as thyroiditis. Percutaneous liver biopsy findings can provide confirmatory information and can assist in the determination of the histologic stage of the disease. The diagnosis and prognosis of PBC are determined best by the results of all of these morphologic and biochemical tests, and imaging findings are considered important to confirm both the absence of biliary obstruction and the presence of cirrhosis and signs of portal hypertension (1,2).

While the clinical features of PBC have been the subject of recent review articles (1,2) and original investigations (4–7), comparatively little is known about the radiologic features of PBC. We have had the opportunity to study a relatively large number of patients who underwent evaluation, treatment, and OLT at this institution.

The purpose of this study was to evaluate and compare clinical, pathologic, and helical computed tomographic (CT) findings of PBC.


   MATERIALS AND METHODS
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
RESULTS
 DISCUSSION
 REFERENCES
 
A retrospective review of medical records from this institution from January 1994 through December 1999 revealed 53 patients (45 women and eight men; age range, 26–71 years; mean age, 50.7 years) who had a diagnosis of PBC and who underwent clinical and helical CT evaluation and orthotopic liver transplantation (OLT) at this medical center. In all patients, the diagnosis of PBC was established on the basis of a combination of gross, histopathologic, immunochemistry, and imaging findings. The study was approved by our institutional review board; patient informed consent was not required.

The epidemiologic data, which were reviewed by one investigator (A.B.), included the patient’s sex, age at the time of diagnosis (which was determined by any means, including laboratory testing and liver biopsy findings), time from diagnosis to OLT, frequency of recurrence of PBC after OLT, and frequency of hepatocellular carcinoma (HCC). From the time of OLT, patients were followed up for an average of 42 months (median, 46 months; range, 5–72 months) to determine the recurrence of PBC or development of HCC.

Pathologic evaluation of the explanted liver was conducted by one of two experienced hepatic pathologists in the liver transplantation unit. One radiologist (A.B.) reviewed the pathology reports for evidence of liver size; surface characteristics; presence and type of fibrosis and regenerating nodules; presence, size, and distribution of lymphadenopathy; and the location, type, and stage of any hepatic malignancy. Histopathologic proof of PBC was based on inflammation and destruction of bile ducts and the presence of hepatic fibrous inflammatory septum formation, patchy infiltrates of inflammatory cells (predominantly lymphocytes and mononuclear leukocytes), and granulomas containing necrotic bile ducts (the florid bile duct lesion) (1,8).

Abdominal lymphadenopathy was recorded when it was evident from findings in reports of surgical observations, pathologic findings, or CT findings and was classified according to location and size. Lymph node enlargement was judged as mild (1.0–1.5 cm), moderate (1.6–2.0 cm), or marked (>2 cm) (9).

The 53 patients had a total of 98 CT scans, and all patients underwent at least one helical multiphase CT evaluation at this institution (HiSpeed or LightSpeed Qxi; GE Medical Systems, Milwaukee, Wis). The patients received 125 or 150 mL of 60% iodinated contrast material (iothalamate meglumine [Conray 60] or ioversol [Optiray 350]; Mallinckrodt Medical, St Louis, Mo) administered with a power injector at a rate of 4 or 5 mL/sec. Nonenhanced and contrast material–enhanced images of the liver were obtained in all cases. Hepatic arterial phase images were obtained with a scanning delay of 25–35 seconds, and portal venous phase images were obtained with a scanning delay of 60-70 seconds. Section thickness was 5 or 7 mm, and pitch was adjusted to permit hepatic scanning in a single breath hold.

All CT findings were reviewed retrospectively by two radiologists (M.P.F., G.B.) by consensus, because we were not attempting to determine the accuracy of CT or individual readers. The readers knew that all patients had PBC, but they had no other information. CT findings that were evaluated included size and contour of the liver, caudate lobe to right lobe ratio (a ratio of greater than 0.6 was considered increased), focal or diffuse atrophy or hypertrophy of the liver or individual hepatic segments, evidence of fibrosis (hypoattenuating areas on nonenhanced scans that appeared patchy or bandlike, lacelike, or confluent, the latter indicating larger areas of low attenuation accompanied by retraction of the hepatic capsule). A subjective evaluation of the degree of cirrhosis and portal hypertension was based on the distortion and volume loss of the liver along with the extent of varices and ascites. Splenomegaly was judged subjectively, although a splenic length of more than 12 cm, a width of 6 cm, or a width of 8 cm was considered excessive.

The liver contour at CT and the liver surface nodularity at pathologic examination were compared with a repeated measures design since multiple CT scans were obtained in some patients. Analysis was performed with a subroutine (PROCMIXED; SAS Institute, Cary, NC). Regenerating nodules were defined as focal hyperattenuating lesions on nonenhanced scans that became isoattenuating to the liver on contrast-enhanced images.

Because we wanted to compare these hepatic morphologic features with the clinical stage of PBC, we defined advanced PBC as that degree of hepatic failure leading to liver transplantation within the subsequent 2 years. Earlier stages were defined as less advanced disease. Although we admit that this is somewhat arbitrary, there is no acceptable clinical classification of the severity of PBC, and we believe that this classification may reflect the disease severity. Of the total 98 CT studies, 21 were in the less advanced group and 77 were in the advanced group. All patients underwent at least one CT study during the advanced stage of disease, and we used findings from these studies for comparison with pathologic findings in the explanted liver. Thirty patients had more than one CT scan (range, 1–5 scans per patient; mean, 1.8 scans per patient; median, 2.0 scans per patient). The time interval between the multiple scans was variable (mean, 13 months; range, 1–60 months). Each scan was separately evaluated for the CT finding criteria noted previously.

Liver volume was determined at CT by means of serial tracing of the circumference of the liver on adjacent CT sections and use of a standard software feature on the workstation (Advantage Windows; GE Medical Systems) to calculate cross-sectional liver areas, which were subsequently summed to determine volume. Volumetric analysis is a standard part of our liver transplant CT evaluation, and it was performed at the time of the initial CT interpretation.

Previous investigators have demonstrated that there is a nearly equal ratio of 1 cm3 of liver volume to 1 g of liver tissue (10) and that liver volume determined at CT accurately reflects physical measures of liver volume and weight (11,12). The normal liver volume is related to the patient’s age and weight, but a volume of 1,493 cm3 (SD, 230 cm3) may be considered normal (12). To determine whether differences between the liver volumes in advanced versus less advanced PBC are statistically significant, we compared the liver volumes evaluated at CT. Analysis was performed with the subroutine because multiple CT scans were obtained in some patients. In addition to these objective measures, we made a subjective judgment of hepatic size relative to patient size, as it is known that liver volume increases in proportion to patient height and weight.


   RESULTS
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
DISCUSSION
 REFERENCES
 
In the 53 patients seen at the time of initial diagnosis of PBC, which often preceded the first CT evaluation, the time from diagnosis to OLT ranged from 0.5 to 20.0 years (mean, 6.1 years). The patients were followed up for 5.4–72.0 months (mean, 42.0 months) after OLT. During the follow-up time, only two patients experienced recurrence of PBC, which was documented at liver biopsy 3 months and 31/2 years after transplantation. HCC was found in the explanted liver of four (8%) patients, but no additional cases of HCC were discovered during the follow-up period.

The weight of the explanted liver ranged from 630 to 3,400 g (mean, 1,512 g). In patients who underwent serial CT studies during more than 5 years, we noted a trend toward decreasing hepatic volume with more advanced disease (Fig 1). The liver volume as determined at CT was smaller in patients with advanced disease (volume range, 547–3,044 cm3; mean, 1,653 cm3; SD, 700 cm3) than in those with less advanced disease (volume range, 613–4,233 cm3; mean, 1,939 cm3; SD, 577 cm3), but the difference was not statistically significant (P = .18). However, some patients with advanced disease had grossly enlarged livers at OLT.



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  		Figure 1a. CT scans show advanced PBC in a 71-year-old woman. (a) Transverse nonenhanced CT scan (narrow window setting) shows lacelike pattern of low-attenuating fibrosis surrounding regenerating nodules (arrows) that are about 1 cm in diameter and are hyperattenuating to normal liver or spleen. The liver volume is 1,300 cm3. (b) Portal venous phase CT scan obtained at the same level as a. The fibrosis and regenerating nodules are no longer evident. Varices are noted, including an enlarged gastroepiploic vein (arrow). (c) Transverse portal venous phase CT scan, obtained at the same level as a and b, was acquired 14 months later, just before OLT. The liver volume has decreased to 1,060 cm3. The liver contour is more nodular, and ascites (A) has developed.

 


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  		Figure 1b. CT scans show advanced PBC in a 71-year-old woman. (a) Transverse nonenhanced CT scan (narrow window setting) shows lacelike pattern of low-attenuating fibrosis surrounding regenerating nodules (arrows) that are about 1 cm in diameter and are hyperattenuating to normal liver or spleen. The liver volume is 1,300 cm3. (b) Portal venous phase CT scan obtained at the same level as a. The fibrosis and regenerating nodules are no longer evident. Varices are noted, including an enlarged gastroepiploic vein (arrow). (c) Transverse portal venous phase CT scan, obtained at the same level as a and b, was acquired 14 months later, just before OLT. The liver volume has decreased to 1,060 cm3. The liver contour is more nodular, and ascites (A) has developed.

 


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  		Figure 1c. CT scans show advanced PBC in a 71-year-old woman. (a) Transverse nonenhanced CT scan (narrow window setting) shows lacelike pattern of low-attenuating fibrosis surrounding regenerating nodules (arrows) that are about 1 cm in diameter and are hyperattenuating to normal liver or spleen. The liver volume is 1,300 cm3. (b) Portal venous phase CT scan obtained at the same level as a. The fibrosis and regenerating nodules are no longer evident. Varices are noted, including an enlarged gastroepiploic vein (arrow). (c) Transverse portal venous phase CT scan, obtained at the same level as a and b, was acquired 14 months later, just before OLT. The liver volume has decreased to 1,060 cm3. The liver contour is more nodular, and ascites (A) has developed.

 
Pathologic evidence of cirrhosis was seen in 52 (98%) of the 53 explanted livers. Cirrhotic liver morphology was evident at CT in the majority of both advanced and less advanced cases of PBC, including heterogeneously attenuating parenchyma and segmental atrophy. The caudate lobe to right lobe ratio was increased on 33 (43%) of 77 images in patients with advanced PBC and on 10 (48%) of 21 images in those with less advanced PBC. Focal or diffuse atrophy was seen on 50 (65%) of 77 images in patients with advanced PBC and on 11 (52%) of 21 images in those with less advanced PBC. Atrophy was diffuse on 23 (30%)of 77 images in patients with advanced disease and on four (19%) of 21 images in those with less advanced disease. Conversely, hypertrophy was seen on 39 (51%) of 77 images in patients with advanced PBC and on 15 (67%) of 21 images in those with less advanced PBC. Hypertrophy of the lateral segment of the left lobe was seen on 30 (39%) of 77 images in patients with advanced PBC and on 12 (57%) of 21 images in those with less advanced PBC. Diffuse hypertrophy was seen on 10 (13%) of 77 images in patients with advanced PBC and on two (10%) of 21 images in those with less advanced PBC.

The explanted livers of 50 (94%) of 53 patients had subcapsular and other regenerating nodules. At CT, 15 (71%) of the 21 images in patients with less advanced PBC demonstrated a smooth contour compared with only 22 (29%) of the 77 images in those with advanced PBC (Figs 2, 3). Conversely, 44 (57%) of the 77 images demonstrated a nodular contour, compared with six (29%) of the 21 images. The diagnosis of surface nodularity at CT correlated with the size of the nodules at pathologic examination. Livers diagnosed as having a nodular contour had a mean nodule diameter of 0.5 cm, whereas livers with a smooth contour had a mean nodule diameter of 0.3 cm, and the difference was significant (P = .04). Other regenerating nodules were demonstrated in 43% of livers in patients in both groups (advanced PBC, 33 of 77 patients; less advanced PBC, nine of 21 patients) (Figs 1, 4).



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  		Figure 2. Transverse portal venous phase CT scan shows less advanced PBC in a 39-year-old woman. The liver is enlarged (2,020 cm3) and has a smooth contour. At biopsy, the patient did not have cirrhosis (no bridging fibrosis), but she already had splenomegaly (S) and varices (arrows). The patient underwent OLT 21/2 years later.

 


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  		Figure 3. Transverse portal venous phase CT scan shows less advanced PBC in a 53-year-old woman. The liver has a smooth contour but widened fissures (F) and hypertrophy of the lateral segment (LS), a dysmorphic appearance indicative of cirrhosis. Splenomegaly and enlarged porta hepatis and portacaval lymph nodes (arrows) are also noted.

 


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  		Figure 4a. Images show advanced PBC in a 69-year-old woman 11 months before OLT. (a) Transverse nonenhanced CT scan (narrow window setting) shows a small (850 cm3) liver with a nodular contour, heterogeneous parenchyma, and hypertrophy of the lateral segment (LS). (b) Transverse portal venous phase CT scan. Marked ascites (A) is noted. Extensive patchy, linear, and confluent fibrosis (arrow) is noted with capsular retraction over the latter. (c) Photograph of explanted liver cut in the transverse plane a few centimeters caudal to the CT sections in a and b. Note the nodular surface and innumerable regenerating nodules (arrows).

 


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  		Figure 4b. Images show advanced PBC in a 69-year-old woman 11 months before OLT. (a) Transverse nonenhanced CT scan (narrow window setting) shows a small (850 cm3) liver with a nodular contour, heterogeneous parenchyma, and hypertrophy of the lateral segment (LS). (b) Transverse portal venous phase CT scan. Marked ascites (A) is noted. Extensive patchy, linear, and confluent fibrosis (arrow) is noted with capsular retraction over the latter. (c) Photograph of explanted liver cut in the transverse plane a few centimeters caudal to the CT sections in a and b. Note the nodular surface and innumerable regenerating nodules (arrows).

 


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  		Figure 4c. Images show advanced PBC in a 69-year-old woman 11 months before OLT. (a) Transverse nonenhanced CT scan (narrow window setting) shows a small (850 cm3) liver with a nodular contour, heterogeneous parenchyma, and hypertrophy of the lateral segment (LS). (b) Transverse portal venous phase CT scan. Marked ascites (A) is noted. Extensive patchy, linear, and confluent fibrosis (arrow) is noted with capsular retraction over the latter. (c) Photograph of explanted liver cut in the transverse plane a few centimeters caudal to the CT sections in a and b. Note the nodular surface and innumerable regenerating nodules (arrows).

 
Some form of fibrosis was evident at pathologic examination in all 53 patients. Both end-stage and earlier forms of PBC demonstrated evidence of some form of fibrosis at CT in the majority of cases. Of the 77 cases of advanced PBC, 25 (32%) had lacelike fibrosis (Fig 1), 23 (30%) had patchy fibrosis, and only two (3%) had confluent fibrosis (Fig 4). In the 21 cases of less advanced PBC, fibrosis was described at CT as lacelike in seven (33%) cases and patchy in five (24%). In only 31 (40%) of the 77 cases of advanced PBC and in 10 (47%) of the 21 cases of less advanced PBC, liver parenchyma was homogeneously attenuating on nonenhanced scans.

CT signs of portal hypertension were more common in advanced PBC, including 88% (n = 68 of 77 cases) with splenomegaly, 87% (n = 67) with varices, and 44% (n = 34) with ascites. Less advanced cases had splenomegaly in 71% (n = 15 of 21 cases), varices in 62% (n = 13), and ascites in 24% (n = 5) (Figs 2, 3).

Lymphadenopathy was noted at surgery in almost all patients, but only selected nodes were submitted for pathologic analysis. Even the four patients with HCC showed benign reactive hyperplasia. CT demonstrated lymphadenopathy in 86 (88%) of 98 patients, most commonly in the portacaval (n = 79 [81%]) and porta hepatis (n = 71 [72%]) regions (Figs 2, 3, 5). Enlarged cardiophrenic (n = 55 [56%]), gastroduodenal (n = 26 [27%]), periaortic (n = 21 [22%],) and peripancreatic (n = 3 [3%]) lymph nodes were less commonly seen. Lymph nodes tended to be smaller in less advanced PBC. Moderate lymph node enlargement (1.5–2.0 cm) was seen in the porta hepatis and portacaval spaces in 30 (38%) and 28 (36%) of 77 patients with advanced PBC, respectively, compared with five (24%) and seven (29%) of 21 patients with less advanced PBC. Marked lymph node enlargement (>2 cm) was seen in the porta hepatis and portocaval spaces in 14 (18%) and 11 (14%) of 77 patients with advanced PBC, respectively, compared with 14% (n = 3) and 10% (n = 2) of 21 patients with less advanced PBC. Differences in lymphadenopathy size or location were not significant in patients with advanced or less advanced PBC. All lymph nodes demonstrated moderate and homogeneous contrast enhancement.



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  		Figure 5. Transverse portal venous phase CT scan shows advanced PBC in a 41-year-old woman, 8 months before OLT. Image demonstrates an enlarged liver (2,300 cm3) without obvious signs of cirrhotic morphology. However, splenomegaly and varices (large arrows) are evident, along with lymphadenopathy (small arrows), in the peripancreatic nodes and elsewhere. PBC recurred within the transplanted liver within 3 months, which is unusually rapid.

 
Four malignancies were documented in the explanted livers, and all were HCC: two were rated as TNM stage I and two as TNM stage IV. Each of the two stage IV tumors had two satellite lesions that were 3.0 and 5.5 cm in maximal diameter. None of the tumors had vascular invasion or lymphatic or distant metastases. Two of the four patients also had chronic hepatitis C infection in addition to PBC. In the two patients with only PBC, the HCC lesions were well-differentiated small (1.3–2.5-cm) tumors that were unexpected findings at the time of OLT. In the two patients with PBC and chronic hepatitis C, the tumors were moderately differentiated and were diagnosed as focal tumor masses (1.2–5.3 cm) on helical CT scans obtained before OLT (Fig 6). Three of the four HCCs were located in the right hepatic lobe. The time from the diagnosis of PBC to the development of HCC was 2–21 years (median, 3 years).



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  		Figure 6. Transverse portal venous phase CT scan shows advanced PBC and chronic hepatitis C in a 67-year-old woman. The liver has a cirrhotic morphology with atrophy of the anterior (AS) and medial (MS) segments and relative enlargement of the caudate lobe. A focal hypoattenuating mass (arrow) represents HCC. The HCC was moderately differentiated, stage II, and did not recur after OLT.

 

   DISCUSSION
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
REFERENCES
 
PBC is an important cause of liver failure in adults and has been the subject of several reviews (1,2). As with other investigations, our study reinforces certain important facets of PBC while calling into question some prior assumptions and conclusions. Dodd et al (13,14) report the radiologic-pathologic findings in 50 patients with PBC who underwent nonhelical CT or MR imaging before liver transplantation. Most of our observations are in concordance with those in that study, although we were able to examine our patients with helical multiphase CT, to study the evolution of hepatic damage during time and the CT characteristics of advanced and less advanced PBC in greater detail.

The natural history of PBC is not fully understood; although the PBC progresses in almost all patients, the rate of progression is variable. In a review (1), it was stated that hepatomegaly is diagnosed clinically in 70% of cases (15) and that it becomes more prominent with progressive PBC. We found, however, that the liver in PBC typically has a normal or increased volume at the time of diagnosis and tends to decrease in volume as the PBC progresses. Some patients with severe portal hypertension (eg, large varices and ascites) and/or end-stage liver disease (requiring transplantation) due to PBC may have an enlarged liver at this stage, an unusual finding among the causes of progressive liver disease (13,14). However, most patients develop global or segmental hepatic atrophy that resembles other types (origins) of end-stage liver disease.

We found diffuse hepatomegaly in six (11%) of our 53 patients, similar to the 12% prevalence reported by Dodd et al (13). In our study, global or segmental hypertrophy was more common in less advanced PBC (66%) than in advanced PBC (51%). Segmental hypertrophy typically involved the lateral and caudate segments of the liver while segmental atrophy disproportionately affected the right lobe and medial segment. These patterns are not unique to PBC but are also seen in viral and alcoholic cirrhosis. (13)

Even before patients with PBC develop CT, histopathologic, or clinical signs of cirrhosis, they may develop signs of portal hypertension (16). Varices may develop and bleed relatively early in the course of PBC, well before jaundice or true cirrhosis are manifested (17,18). We found CT evidence of varices in 62% of patients with less advanced PBC and in 87% of those with advanced PBC. Ascites, usually considered a late manifestation of cirrhosis, was demonstrated in 24% of our patients with less advanced cases and in 44% of those with advanced PBC. Splenomegaly is diagnosed at physical examination in about 35% of patients (1), while we found CT evidence of splenomegaly in 71% and 88% of patients with less advanced and advanced PBC, respectively. Our results show that CT can demonstrate objective signs of portal hypertension due to PBC that may not be as evident with other means of clinical testing.

Fibrosis is an inherent part of hepatic cirrhosis, and it was a prominent feature in other studies and in ours (13,14). Fibrosis is best visualized on nonenhanced CT scans and is usually not well visualized on portal venous phase images. We found several patterns of fibrosis, including the lacelike pattern of thin or thick bands of low attenuation that surround regenerating nodules. This pattern was seen in about one-third of our patients with PBC, regardless of stage, and seems to be characteristic of PBC. Patchy poorly defined regions of low attenuation believed to represent fibrosis were almost as common a pattern, but they were noted slightly more frequently in advanced PBC. Confluent hepatic fibrosis was seen on only two of our 98 CT scans, both depicting advanced PBC.

Both the overall hepatic size and parenchymal heterogeneity may evolve over the course of PBC. As noted by Kaplan (1, p 1570), "The liver in patients with PBC is characteristically enlarged and smooth ... . As the disease progresses, the liver ... becomes more nodular and eventually appears grossly cirrhotic." We found a smooth liver contour in 71% of cases of less advanced PBC but in only 43% of cases OF advanced PBC. Conversely, CT showed a nodular contour in 29% and 57% of cases of less advanced and advanced PBC, respectively. The regenerative nodules responsible for the nodular contour are not easily demonstrated at CT but are best visualized as small spheric hyperattenuating foci on nonenhanced scans that are isoattenuating to liver on portal venous phase images. We identified regenerative nodules in 43% of all our cases, compared with 52% in the study of Dodd et al (14).

The frequency and clinical importance of lymphadenopathy in PBC have been the subject of considerable interest and some controversy (9,19–24). While some early reports suggest that lymphadenopathy in PBC is uncommon and might be considered suggestive of underlying malignancy (19), more recent work presents convincing evidence to the contrary (9,21). In another study by Dodd et al (9), abdominal lymphadenopathy was seen in 86% of patients with PBC compared with 37%–49% of patients with other forms of cirrhosis. Our results were almost identical, documenting lymphadenopathy in 88% of our patients, most commonly found in the porta hepatis and portacaval spaces. The surgically removed and sampled nodes in patients undergoing OLT have invariably demonstrated benign reactive hyperplasia, even in patients with an underlying hepatic malignancy. Even nodal groups often associated with disseminated malignancy, such as cardiophrenic and periaortic nodes, are often enlarged owing to benign hyperplasia in PBC.

As suggested by other investigators (21,22), we noted a trend toward increased nodal size with more advanced PBC, although this is of uncertain clinical importance. Some investigators have found a positive correlation between the extent of lymphadenopathy and various histopathologic and laboratory parameters of hepatocellular damage in PBC (24), while others have not (21). We doubt that the extent of lymphadenopathy demonstrated at CT can play an important role in determining the prognosis or treatment of patients with PBC.

The frequency of HCC is increased markedly in certain types of cirrhosis, especially that due to chronic hepatitis B or C. Early reports suggest that patients with PBC are at no increased risk for developing HCC (24,25), but other investigations (25–31) suggest an increased frequency ranging from 0.5% to 7.5%. The frequency probably depends on numerous factors, including longer patient survival before OLT and coexistence of diseases, especially viral hepatitis. Four of our 53 (8%) patients had HCC at the time of OLT; two of these had concomitant hepatitis C and two had only PBC. HCC in PBC tends to be well differentiated and may be an incidental or unexpected finding at OLT, as in two of our patients. Helical multiphase CT offers greater accuracy in the detection and staging of HCC compared with transverse CT (32). A low-grade and low-stage HCC is not considered a contraindication or even a bad prognostic factor for liver transplantation in this setting (33,34).

Liver transplantation clearly improves the survival and quality of life for patients with advanced PBC (6,30). The 1-year survival rate has increased to 90%, and subsequent survival rates resemble those of healthy patients matched for age and sex (1). Timing of the OLT is considered to be one of the most difficult clinical decisions, and many investigators have attempted to determine useful prognostic factors (5,35–37). Among the important criteria are the patient’s age; laboratory parameters, such as serum bilirubin level and prothrombin time; and various histopathologic findings (5,35–37). As noted previously, clinical and laboratory parameters do not always parallel each other in PBC. We found that CT can demonstrate important features, such as varices and ascites, before these or other clinical signs of cirrhosis are evident to referring physicians. CT can also provide important morphologic information about the liver itself, including its size and the presence or absence of HCC, and other pretransplantation assessments, such as the status of the major hepatic blood vessels.

PBC can recur after transplantation (8,38–46) but with a frequency much lower than that for hepatitis and other diseases. The reported frequency of recurrence varies widely, is influenced by the type of immunosuppression therapy, and clearly increases over time. The recurrence rate seems to be about 1%–2% per year of survival after OLT, which is consistent with our rate of 4% (recurrence in two patients at 3 months and 31/2 years after transplantation).

In conclusion, PBC is an important cause of liver failure in adults, and it has certain characteristic morphologic and pathophysiologic features that are demonstrated well at CT. Because of the variability in clinical course and the discordance in results between certain tests of hepatic functions in PBC, CT may offer important information in evaluation and surveillance of these patients.


   FOOTNOTES
 
Abbreviations: HCC = hepatocellular carcinoma, OLT = orthotopic liver transplantation, PBC = primary biliary cirrhosis

Author contributions: Guarantor of integrity of entire study, M.P.F.; study concepts, M.P.F.; study design, M.P.F., A.B.; literature research, A.B.; clinical studies, M.P.F., G.B.; data acquisition, A.B., M.P.F., G.B.; data analysis/interpretation and statistical analysis, A.B.; manuscript preparation, M.P.F., A.B.; manuscript definition of intellectual content, editing, and revision/review, M.P.F.; manuscript final version approval, A.B., M.P.F., G.B.


   REFERENCES
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 

  1. Kaplan MM. Medical progress: primary biliary cirrhosis. N Engl J Med 1996; 335:1570-1580.[Free Full Text]
  2. Mahl TC, Slockcar W, Boyer JL. Primary biliary cirrhosis: survival of a large cohort of symptomatic patients followed for 24 years. J Hepatol 1994; 20:707-713.[CrossRef][Medline]
  3. Van de Water J, Cooper A, Surh CD, et al. Detection of antibodies to recombinant mitochondrial proteins in patients with primary biliary cirrhosis. N Engl J Med 1989; 320:1377-1380.[Abstract]
  4. Magrini A, Nicodemo S, Puoti C. Hospital prevalence of asymptomatic primary biliary cirrhosis: 4 year study based on analysis of 4468 consecutive in-patients. Liver 1996; 16:377-379.[Medline]
  5. Goudie BM, Burt AD, Macfarlane GJ, et al. Risk factors and prognosis in primary biliary cirrhosis. Am J Gastroenterol 1989; 84:713-716.[Medline]
  6. Wiesner RH, Porayko MK, Dickson ER, et al. Selection and timing of liver transplantation in primary biliary cirrhosis and primary sclerosing cholangitis. Hepatology 1992; 16:1290-1299.[CrossRef][Medline]
  7. Howel D, Fischbacher CM, Bhopal RS, Gray J, Metcalf JV, James OF. An exploratory population based case control study of primary biliary cirrhosis. Hepatology 2000; 31:1055-1060.[CrossRef][Medline]
  8. Portmann BC. Recurrence of primary biliary cirrhosis after transplantation: the pathologist’s view. Eur J Gastroenterol Hepatol 1999; 11:633-637.[Medline]
  9. Dodd GD, Baron RL, Oliver JH, Federle MP, Baumgartel PB. Enlarged abdominal lymph nodes in end-stage cirrhosis: CT and histopathologic correlation in 507 patients. Radiology 1997; 203:127-130.[Abstract/Free Full Text]
  10. Soyer PH, Roche A, Elias D, Levesque M. Hepatic metastases from colorectal cancer: influence of hepatic volumetric analysis on surgical decision. Radiology 1992; 184:695-697.[Abstract/Free Full Text]
  11. Heymsfield SB, Fulenwider T, Nordlinger B, Barlow R, Sones P, Kutner MH. Accurate measurement of liver, kidney and spleen volume and mass by computerized axial tomography. Ann Intern Med 1979; 90:185-187.
  12. Henderson JM, Heymsfield SB, Horowitz J, Kutner MH. Measurement of liver and spleen volume by computed tomography. Radiology 1981; 141:525-527.[Abstract/Free Full Text]
  13. Dodd GD, Baron RL, Oliver JH, Federle MP. Spectrum of imaging findings of the liver in end stage cirrhosis. I. Gross morphology and diffuse abnormalities. AJR Am J Roentgenol 1999; 173:1031-1036.[Free Full Text]
  14. Dodd GD, Baron RL, Oliver JH, Federle MP. Spectrum of imaging findings of the liver in end stage cirrhosis. II. Focal abnormalities. AJR Am J Roentgenol 1999; 173:1185-1192.[Abstract/Free Full Text]
  15. Long RG, Scheuer PJ. The presentation and course of asymptomatic primary biliary cirrhosis. Gastroenterology 1977; 72:1204-1207.[Medline]
  16. Colina F, Pinedo F, Solis JA, Moreno D, Nevado M. Nodular regenerative hyperplasia of the liver in early histological stages of primary biliary cirrhosis. Gastroenterology 1992; 102:1319-1324.[Medline]
  17. Thornton JR, Triger DR, Losowsky MS. Variceal bleeding is associated with reduced risk of severe cholestasis in primary biliary cirrhosis. Q J Med 1989; 71:467-471.[Abstract/Free Full Text]
  18. Navasa M, Pares A, Bruguera M, Caballeria J, Bosch J, Rodes J. Portal hypertension in primary biliary cirrhosis: relationship with histological features. J Hepatol 1987; 5:292-298.[CrossRef][Medline]
  19. Eustace S, Buff B, Kane R, Jenkins R, Longmaid HE. The prevalence and clinical significance of lymphadenopathy in primary biliary cirrhosis. Clin Radiol 1995; 50:396-399.[CrossRef][Medline]
  20. Molmenti EP, Ford K, Wenzel J, et al. Primary biliary cirrhosis: MRI findings in 21 consecutive pretransplant patients, and description of "MRI periportal halo" sign (abstr). Presented at the International Liver Transplantation Society Congress, Buenos Aires, Argentina June 21–23, 2000.
  21. Dietrich CF, Leuschner MS, Zeuzem S, et al. Peri-hepatic lymphadenopathy in primary biliary cirrhosis reflects progression of the disease. Eur J Gastroenterol Hepatol 1999; 11:747-753.[Medline]
  22. Kathrein H, Judmaier G, Vogel W. Lymphadenopathy in primary biliary cirrhosis: CT observations (letter). Radiology 1990; 175:285.[Free Full Text]
  23. Cassani F, Valentini P, Cataleta M, et al. Ultrasound detected lymphadenopathy in chronic hepatitis C: high frequency and relationship with viremia. J Hepatol 1997; 26:479-483.[CrossRef][Medline]
  24. Lyttkens K, Prytz H, Forsberg L, Hederstrom E, Hagerstrand I. Ultrasound, hepatic lymph nodes and primary biliary cirrhosis. J Hepatol 1992; 15:136-139.[CrossRef][Medline]
  25. Morimoto T, Honda G, Kawai Y, et al. Right hepatic lobectomy for hepatocellular carcinoma which developed in primary biliary cirrhosis: report of a case. Jpn J Surg 1999; 29:646-650.
  26. Wakai T, Shirai Y, Tsukada K, Aono T, Kurosaki I, Hatakegama K. Hepatocellular carcinoma associated with precirrhotic primary biliary cirrhosis successfully treated by a right hepatic lobectomy: report of a case. Jpn J Surg 1996; 26:723-726.
  27. Loof L, Adami HO, Sparen P, et al. Cancer risk in primary biliary cirrhosis: a population based study from Sweden. Hepatology 1994; 20:101-104.[CrossRef][Medline]
  28. Witt-Sullivan H, Heathcote J, Cauch K, et al. The demography of primary biliary cirrhosis in Ontario, Canada. Hepatology 1990; 12:98-105.[Medline]
  29. Farinati F, Floreani A, Maria N, Fagiuoli S, Naccarato R, Chiaramonte M. Hepatocellular carcinoma in primary biliary cirrhosis. J Hepatol 1994; 21:315-316.[CrossRef][Medline]
  30. Locke GR, Dickson R. Transplantation for primary biliary cirrhosis. In: Busuttil RU, Klintmalm GB, eds. Transplantation of the liver. Philadelphia, Pa: Saunders, 1996; 101-107.
  31. Nakanuma Y, Terada T, Doishita K, Miwa W. Hepatocellular carcinoma in primary biliary cirrhosis: an autopsy study. Hepatology 1990; 11:1010-1016.[Medline]
  32. Baron RL, Oliver JH, III, Dodd GD, III, Nalesnik M, Holbert BL, Carr B. Hepatocellular carcinoma: evaluation with biphasic contrast-enhanced helical CT. Radiology 1996; 199:505-511.[Abstract/Free Full Text]
  33. Marsh JW, Casavilla A, Iwatsuki S, et al. Predicting the risk of tumor recurrence following transplantation for HCC. Hepatology 1997; 26:89-91.[CrossRef]
  34. Marsh JW, Dvorchik I, Bonhan CA, Iwatsuki S. Is the pathologic TNM staging system for patients with hepatoma predictive of outcome?. Cancer 2000; 88:538-543.[CrossRef][Medline]
  35. Roll J, Boyer JL, Barry D, Klatskin G. The prognostic importance of clinical and histological features in asymptomatic and symptomatic biliary cirrhosis. N Engl J Med 1983; 308:1-7.[Abstract]
  36. Dickson ER, Grambsch PM, Fleming TR, Fisher LD, Langworthy A. Prognosis in primary biliary cirrhosis: a model for decision making. Hepatology 1989; 10:1-7.[Medline]
  37. Rydning A, Schrumpf E, Abdelnoor M, Elgjo K, Jenssen E. Factors of prognostic importance in primary biliary cirrhosis. Scand J Gastroenterol 1990; 25:119- 126.[Medline]
  38. Papo O, Ramos H, Starzl T, Fung JJ, Demetris AJ. Structural integrity and identification of liver allograft dysfunction occurring more than 5 years after transplantation. Am J Surg Pathol 1995; 19:192-206.[Medline]
  39. Sebagh M, Farges O, Dubel L, Samuel D, Bismuth H, Regnes M. Histological features predictive of recurrence of primary biliary cirrhosis after liver transplantation. Transplantation 1998; 65:1328-1333.[CrossRef][Medline]
  40. Jones EA. Primary biliary cirrhosis and liver transplantation (editorial). N Engl J Med 1982; 306:41-42.[Medline]
  41. Neuberger J, Portman B, Macdougal BRD. Recurrence of primary biliary cirrhosis after liver transplantation. N Engl J Med 1982; 306:1-4.[Abstract]
  42. Haagsma EB. Clinical relevance of recurrence of primary biliary cirrhosis after liver transplantation. Eur J Gastroenterol Hepatol 1999; 11:639-642.[Medline]
  43. Balan V, Batts KP, Porayko MK, Krom RA, Ludwig J, Wiesner RH. Histological evidence for recurrence of primary biliary cirrhosis after liver transplantation. Hepatology 1993; 18:1392-1398.[CrossRef][Medline]
  44. Gouw AS, Haagsma EB, Manns M, Klompmaker IJ, Slooff MJ, Gerber MA. Is there recurrence of primary biliary cirrhosis after liver transplantation? a clinicopathological study in long term survivors. J Hepatol 1994; 20:500-507.[CrossRef][Medline]
  45. Hubscher SG, Elias E, Buckels JAC, Mager AD, McMaster P, Neuberger JM. Primary biliary cirrhosis: histological evidence of disease recurrence after liver transplantation. J Hepatol 1993; 18:173-184.[CrossRef][Medline]
  46. Dmitrewski J, Hubscher SG, Mayer AD, Neuberger JM. Recurrence of primary biliary cirrhosis in the liver allograft: the effect of immunosuppression. J Hepatol 1996; 24:253-257.[CrossRef][Medline]



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